Caspase-3 is a protease activated during apoptosis in normal development, cancer prevention, and aberrantly in disease states including ischemia, many forms of cancer, Alzheimer's and Parkinson's. Regulation of caspase-3 is a currently a goal in drug discovery. However as I am discovering and present below in preliminary evidence and planned experiments, caspase-3 appears to have a role in normal memory formation. Here I show preliminary evidence that active caspase-3 becomes present at 2 min, peaks at 10 min and is gone by 20 min in the auditory memory encoding region NCM of adult male zebra finches. This very rapid and transient activation is wide spread throughout NCM and does not lead to cell death. On going Imaging studies show this activation to be localized to the post-synaptic dendritic spine. Importantly preliminary evidence shows that when caspase-3 is inhibited the birds do not form auditory memories suggesting targeting of this enzyme with drugs may have drastic consequences on normal neuronal functioning. As well, it is strongly supportive of the hypothesis that synaptic depression, loss of function, is required for memory formation. This is, as far as I know, the first major piece of evidence to place an activation of caspase-3 at a potential site of active memory storage in a behaving animal. Here I outline a plan of research to further describe this novel and rapid activation of caspase-3 by both histological and molecular techniques. I will be using the emerging model system for the study of memory formation: the adult zebra finch as it responds to novel conspecific bird song. Working Hypothesis: Playback of novel songs will trigger a transient activation of caspase-3, at subcellular sites supporting the storage of new song memories, in the zebra finch caudomedial neostriatum (NCM, auditory